Diversity-generating retroelements (DGRs) create vast amounts of targeted, functional diversity by facilitating the rapid evolution of ligand-binding protein domains. Thousands of DGRs have been identified in bacteria, archaea, and their respective viruses. They are broadly distributed throughout the microbial world, with enrichment observed in certain taxa and environments. The diversification machinery works through a novel mechanism termed mutagenic retrohoming, whereby nucleotide sequence information is copied from an invariant DNA template repeat (TR) into an RNA intermediate, selectively mutagenized at TR adenines during cDNA synthesis by a DGR-encoded reverse transcriptase, and transferred to a variable repeat (VR) region within a variable-protein gene ( 54 ). This unidirectional flow of information leaves TR-DNA sequences unmodified, allowing for repeated rounds of mutagenic retrohoming to optimize variable-protein function. DGR target genes are often modular and can encode one or more of a wide variety of discrete functional domains appended to a diversifiable ligand-binding motif. Bacterial variable proteins often localize to cellsurfaces, although a subset appear to be cytoplasmic, while phage-encoded DGRs commonly diversify tail fiber–associated receptor-binding proteins. Here, we provide a comprehensive review of the mechanism and consequences of accelerated protein evolution by these unique and beneficial genetic elements.

中文翻译：

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产生多样性的逆转录因子加速进化

多样性生成逆转录元件（DGR）通过促进配体结合蛋白结构域的快速进化，创造大量有针对性的功能多样性。已在细菌、古细菌及其各自的病毒中发现了数以千计的 DGR。它们广泛分布在整个微生物世界中，在某些类群和环境中观察到富集。多样化机制通过一种称为诱变回归的新机制发挥作用，其中核苷酸序列信息从不变的 DNA 模板重复序列 (TR) 复制到 RNA 中间体中，在 cDNA 合成过程中通过 DGR 编码的逆转录酶在 TR 腺嘌呤处选择性诱变，并转移至可变蛋白基因内的可变重复（VR）区域（54）。这种单向信息流使 TR-DNA 序列保持不变，从而允许重复轮次诱变回归以优化可变蛋白功能。 DGR 靶基因通常是模块化的，可以编码附加到可多样化配体结合基序上的一个或多个离散功能域。细菌可变蛋白通常定位于细胞表面，尽管其中一部分似乎位于细胞质中，而噬菌体编码的 DGR 通常使尾纤维相关受体结合蛋白多样化。在这里，我们对这些独特且有益的遗传元件加速蛋白质进化的机制和后果进行了全面的回顾。